Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells

Abstract

Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

“…Vadevoo et al reported that they synthesized an IL4R-targeting peptide (IL4RPep-1-K) conjugated with the proapoptotic peptide (KLAKLAK)2 and demonstrated this peptide exerted the selective anti-cancer effect against IL4R-expressing tumor in vitro and in vivo (4T1 breast tumor-bearing mice model) [11]. In fact, our laboratory has been developing the novel drug delivery system using ultrasound and microbubble-liposome complex with IL4RPep-1-K to detect and treat IL4R-expressing tumor [66].…”

Recent Progress in Bioconjugation Strategies for Liposome-Mediated Drug Delivery

“…Peptide-liposome bioconjugate systems can often be combined and used with other technologies for a dual-purpose drug delivery system. Park and colleagues established a novel microbubble-liposome complex conjugated to interleukin-4 receptor (IL4R)-targeting peptide ligands for theranostic treatment of brain tumors ( Figure 6A) [112]. In this study, DSPE-PEG-PDP liposomes were prepared using thin-film hydration and remote-loaded with DOX via an ammonium sulfate gradient.…”

An ultrasound‐responsive dual‐modal US/T1‐MRI contrast agent for potential diagnosis of prostate cancer

“…Microbubbles (micrometer-sized bubbles, MBs) and melanin nanoparticles (MNPs) are emerging biocompatible materials for the diagnosis of various diseases and represent a safer and more effective alternative to conventional contrast agents. 16 MBs are generally composed of a hydrophobic gas-filled core and shell of lipids. They can generate echogenicity with US at a certain frequency owing to the absorption and reflection property of US waves and nonlinear oscillation.…”

“…Microbubbles (micrometer‐sized bubbles, MBs) and melanin nanoparticles (MNPs) are emerging biocompatible materials for the diagnosis of various diseases and represent a safer and more effective alternative to conventional contrast agents . MBs are generally composed of a hydrophobic gas‐filled core and shell of lipids.…”